Biological plausibility and preliminary evidence suggest that vitamin D may affect prostate cancer risk. We propose to conduct a case-control study to investigate the role of plasma levels of vitamin D and the vitamin D receptor (VDR) gene in the etiology of prostate cancer. Cases will be men aged 65-79 with histologically confirmed prostate cancer. They will be ascertained from the Cancer Surveillance Program a population-based cancer registry that covers Los Angeles County. There will be 170 African/American and 170 White men with advanced prostate cancer and 170 African-American and 170 White men with localized prostate cancer. Controls will be ascertained from the Health Care Financing Administration (HCFA) files. They will be matched to cases by race, age and zip code. Subjects will provide one sample of blood, drawn at their homes, and will complete a short questionnaire about demographic variables and ethnicity. From the blood sample, we will determine a) plasma levels of vitamin D both 25(OH)D and 1,25(OH)2D; b) alleles of the BsmI polymorphism of the VDR gene; c) changes in the 3 untranslated region (UTR) of the VDR mRNA. We also propose to conduct studies of site- directed mutagenesis of the changes in the 3'UTR, to determine the functional effects of these changes on VDR expression and identify which changes are more likely to have effects on prostate cancer. These data will enable us to determine the main effects of plasma vitamin D and alleles of the VDR locus on risk of prostate cancer and to explore possible interactions between plasma levels of vitamin D and the VDR locus that may affect the action of vitamin D.